TALENT, a national lung cancer screening study conducted in Taiwan in 12,011 individuals, uncovered the presence of lung cancer in 2.6% of the study population (Abstract PS01.02). These results are striking, not only because they exceed the 1.1% and 0.9% lung cancer detection rates documented in the US National Lung Screening Trial1 and the NELSON trial,2 respectively, but because the study was conducted in high-risk never-smokers as opposed to heavy smokers.
“Lung cancer in never-smokers is a global rising threat. The pathogenic mechanism and method of screening may be different” for individuals who do not smoke versus those who do, stated Pan-Chyr Yang, MD, PhD, of the National Taiwan University College of Medicine, who presented the TALENT findings during the Presidential Symposium.
Lung cancer is the leading cause of cancer-related mortality in Taiwan, and 53% of these deaths occur among never-smokers. Although smoking remains very low among women in Taiwan and smoking-cessation campaigns have dramatically reduced smoking among men, the incidence of lung adenocarcinoma continues to rise, suggesting other causative factors aside from smoking.
Dr. Yang explained that lung cancer among never-smokers in East Asia represents a distinct disease. “The genomic profile, the carcinogenesis, and the pattern of progression are different” when compared with individuals who smoke.
Given that low-dose computed tomography (LDCT) screening of heavy smokers succeeds in catching lung cancer early and reducing mortality, Dr. Yang and colleagues designed the TALENT study with the aim of developing a similarly effective screening strategy for never-smokers at high risk for disease.
The study was open to individuals aged 55 to 75 years with a negative chest x-ray and any of the following high-risk features: a family history of lung cancer that included first-, second-, or third-degree relatives; environmental smoking exposure; a history of chronic lung disease, such as tuberculosis or chronic obstructive pulmonary disease; cooking without ventilation; and a cooking index of 110 or greater (defined as 2/7 x the number of days of frying per week x the number of years cooking). Younger individuals could participate in the study if they had a family history of lung cancer.
Notably, 73.8% of the study population were women, the average age of individuals was 61.2 years, and 50.0% had a family history of lung cancer. In addition, 93.3% of individuals had never smoked, whereas the other 6.7% had smoked less than 10 pack-years and quit more than 15 years ago.
All individuals underwent LDCT followed the protocol modified from the guidelines established by the American College of Radiology from February 2015 to July 2019. Solid or part-solid nodules larger than 6 mm in diameter or pure ground glass nodules larger than 5 mm in diameter were considered positive.
Of the 12,011 scans performed, 2,094 (17.4%) were considered positive. A total of 392 individuals (3.3%) underwent lung biopsy or surgery, leading to a lung cancer diagnosis in 311 (2.6%). Of these 311 individuals, 254 had invasive disease, leading to a 2.1% prevalence of invasive lung cancer in the overall population.
Importantly, 96.5% of the patients diagnosed with lung cancer had stage 0 or I disease, providing the opportunity for curative resection. In addition, all lung cancers identified, except for one, were adenocarcinomas.
In seeking to determine which factors posed the highest risk for lung cancer among the never-smoker population, family history rose to the top of the list. The prevalence of lung cancer was 3.2% in patients with a family history of the disease compared with a prevalence of 2.0% in those without—a significant difference between groups (P < 0.001). The same trend emerged for invasive lung cancer, with a 2.6% prevalence among individuals with a family history compared with a prevalence of 1.6% among those without.
Although a lung cancer family history was associated with a higher likelihood of finding lung cancer in screened individuals, not all family history was the same. The strength of the blood ties played a key role. The prevalence of lung cancer decreased as affected family members became more removed, as illustrated by rates of 3.3%, 1.6%, and 1.7% among those with affected first-, second, and third-degree relatives, respectively. Moreover, the more first-degree relatives with lung cancer, the higher the likelihood of lung cancer detection among the screened individuals (Figure).
Aside from family history, none of the other high-risk factors used as entry criteria—environmental tobacco exposure, a history of chronic lung disease, cooking without ventilation, and a cooking index of 110 or greater—were significantly associated with a higher risk for lung cancer detection.
Based on the TALENT findings, Dr. Yang concluded that “LDCT lung cancer screening for never-smokers with high risk may be feasible,” although long-term data are needed to determine whether screening these individuals leads to lower lung cancer mortality.
Ugo Pastorino, MD, of the Instituto Nazionale Tumori in Milan, Italy, largely agreed with this conclusion. “The take-home message of the study is that TALENT provides new, very original evidence of lung cancer risk. Therefore, the lung cancer screening eligibility could be redefined in Asia, or at least in Eastern Asia,” he said.
Moving forward, Dr. Pastorino would like to see more research devoted to understanding the biology of lung cancer nonsmokers. On this note, he mentioned recent research from Dr. Yang and colleagues on the proteogenomics of nonsmoking lung cancer in East Asia.3
“This study discloses different genetic susceptibility and exogenous mutational processes that may contribute to the epidemiology that we have seen in Taiwanese females. In particular, the APOBEC mutation profile can be one of the causes of the family risk observed in the Taiwanese population,” he suggested.
National Lung Screening Trial Research Team, Church TR, Black WC, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):1980-1991.
de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382(6):503-513.
Chen YJ, Roumeliotis TI, Chang YH, et al. Proteogenomics of non-smoking lung cancer in East Asia delineates molecular signatures of pathogenesis and progression. Cell. 2020;182(1):226-244.e17.